How newts can help osteoarthritis patients

Posted on 20 August 2015

Scientists at the University of York have taken a leaf out of nature’s book in an attempt to develop effective stem cell treatment for osteoarthritis, a condition which affects millions of people in the UK alone.

Red-spotted Newt (Notophthalmus viridescens)

A research team at York has adapted the astonishing capacity of animals such as newts to regenerate lost tissues and organs caused when they have a limb severed.

The research, which is funded by a £190,158 award from the medical research charity Arthritis Research UK, is published in NatureScientific Reports.

The scientists, led by Dr Paul Genever in the Arthritis Research UK Tissue Engineering Centre in the University’s Department of Biology, have developed a technique to rejuvenate cells from older people with osteoarthritis to repair worn or damaged cartilage thus reducing pain.

There is currently no treatment to prevent the progression of osteoarthritis, and people with severe disease often need total joint replacement surgery.

A patient’s own bone marrow stem cells are, however, a valuable source of potential treatment as they can generate joint tissue the body will not reject when re-implanted. Nevertheless, as people grow older the number of stem cells decreases and those that remain are less able to grow and repair tissue.

Cells in newts can change in response to injury -- a process known as dedifferentiation. The cells aggregate and return to a stem cell-like state to allow them to increase in numbers and generate the specialised cells needed for new tissue formation

But this form of tissue regeneration does not occur in humans, so the researchers recreated similar conditions in the laboratory by growing human cells as 3D aggregates.

The scientists cultivate the spheroid clusters of cells, which are just visible to the naked eye, in tiny cavities. The process involves reverting cells to an embryonic state. In doing so, the cells eat their own constituents and consequently reduce in size.

Dr Genever said: “Using this technique, we have shown that human cells can also be dedifferentiated to an early embryonic stage. They are then capable of generating new tissues. We were able to use pharmaceuticals to induce cell self-eating effects and stimulate dedifferentiation though not as effectively as 3D culture, so we need to do more work on this.

“The next stage is to find out more about the dedifferentiation process so that we can find the right treatment to encourage tissue repair in the damaged joint. That is our aim.”

Lead author, Dr Rebecca Pennock, who worked on the study at the University of York, is funded by Arthritis Research UK and previously by the Biotechnology and Biological Sciences Research Council. The research also involved scientists in the Hull York Medical School Centre for Cardiovascular and Metabolic Research at the University of Hull.

Osteoarthritis is the most common form of joint disease worldwide. In the UK, around a third of people aged 45 years and over, totalling 8.75 million people, have sought treatment from their GP for the condition. The condition causes pain and stiffness in the joints due to cartilage at the ends of bones wearing away.

Dr Stephen Simpson, director of research and programmes at Arthritis Research UK added: “This is exciting, novel work in the field of regenerative medicine, which although in its early experimental stages, could take us a step closer to our ultimate goal of a more effective and much-needed new treatment for the very many people who live with this painful joint condition.”

Arthritis Research UK is the charity dedicated to stopping the devastating impact that arthritis has on people’s lives. Its remit covers all conditions that affects the joints, bones and muscles, including osteoarthritis, rheumatoid arthritis, back pain and osteoporosis. It funds research into the cause, treatment and cure of arthritis, provides information on how to maintain healthy joints and bones and to live well with arthritis. It also champions the cause, influences policy change and works in partnership with others to achieve its aims, and depends on public support and the generosity of donors.

Further information:

The paper ‘Human cell dedifferentiation in mesenchymal condensates through controlled autophagy’ is published in Nature Scientific Reports. www.nature.com/articles/srep13113